ClinicalTrials.gg
Sign In
Status unknownNCT03603951Updated Oct 1, 2024

A Phase 1 Study of SHR2554 in Subjects With Relapsed or Refractory Mature Lymphoid Neoplasms

A Phase 1 interventional study of SHR2554 in Relapsed or Refractory Mature Lymphoid Neoplasms, sponsored by Jiangsu HengRui Medicine Co., Ltd.. Status unknown at 1 site in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2024-10-01.

Sponsored by Jiangsu HengRui Medicine Co., Ltd. · Phase 1, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Sep 2024), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Phase 1
Study type
Interventional
Enrollment
272
Allocation
Not applicable
Ages
18 Years to 70 Years
Sex
All
01

Study summary

This is a Phase 1 multicenter, single-arm, open-label, dose escalation and dose expansion study of enhancer of zeste homolog 2 (EZH2 ) inhibitor SHR2554.

This study will assess the tolerability, safety, pharmacokinetics, and preliminary anti-tumor activity of SHR2554 in participants with relapsed or refractory mature lymphoid neoplasms in part I, and the the efficacy in PTCL patients will be studied in Part II.

02

Conditions studied

  • Relapsed or Refractory Mature Lymphoid Neoplasms

Browse trials for

Keywords

  • SHR2554
  • EZH2 inhibitor
  • phase 1
  • mature lymphoid neoplasm
03

In context

Recurrence

4,347 studies on the registry are indexed under Recurrence; 1,004 are open to participants now.

This study's enrollment of 272 is above the median of 50 across 3,429 interventional studies indexed under Recurrence.

Browse Recurrence studies →

Lead sponsor

Jiangsu HengRui Medicine Co., Ltd. is the lead sponsor of 570 studies on the registry; 85 are open to participants now.

Of its 10 completed or terminated interventional studies of FDA-regulated products, 1 (10%) have results posted.

Browse Jiangsu HengRui Medicine Co., Ltd. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. 18 to 70 years old (Adult, Senior)
  2. Part I: Histologically or cytologically confirmed Mature lymphoid neoplasms; Part II: peripheral T cell lymphomas
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；
  4. Has a life expectancy of ≥12 weeks；
  5. Resistant to standard therapy or no standard therapy available，have indications for treatment；
  6. Have measurable disease （lymphoma participants，any nodes/nodal masses>1.5 cm in longest diameter (LDi) or extralymphatic sites of disease >1.0 cm in LDi；Multiple myeloma (MM) or Waldenström macroglobulinemia (WM) participants，serum M protein ≥0.5 g/dL or Bence Jones protein≥0.2 g/24 h）. （dose expansion study must satisfy）
  7. Has sufficient tumor tissue (slides or blocks) available for testing EZH2 mutation status and expression level. （dose expansion study must satisfy）
  8. Diffuse large B-cell lymphoma (DLBCL) participants have immunohistochemistry test results of cell origin (germinal center B-cell-like (GCB) or non-GCB), as well as myelocytomatosis oncogene (MYC), B cell lymphoma/leukemia 2 (BCL2) and B-cell lymphoma 6 (BCL6), or provide sufficient tumor tissue for testing. （dose expansion study must satisfy）
  9. With adequate bone marrow function;
  10. With adequate renal and liver function;
  11. Coagulation function index：PT ≤1.5×ULN，APTT ≤1.5×ULN；
  12. Women of childbearing potential (WOCBP) should be proven to be negative by human chorionic gonadotropin (hCG) test in 7 days before the first dose of SHR2554. They must be willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy from the day they sign the informed consent form (ICF) to at least 30 days after receiving the last dose of study treatment. Male subjects with WOCBP partner should receive Surgical sterilization or consent to employ a highly effective method of birth control/contraception to prevent pregnancy；
  13. Any prior treatment-related clinically significant toxicities have resolved to ≤ Grade 1 per CTCAE version 4.03 or prior treatment-related toxicities evaluated by physicians are not clinically significant at time of enrollment.
  14. Participant who has provided written consent to participate in the study and ability to comply with all aspects of the protocol.

Exclusion criteria

Exclusion Criteria:

  1. Prior exposure to other inhibitor(s) of EZH2.
  2. FL 3b or (potentially) transformed FL
  3. Participants with a presence of central nerves invasion
  4. Auto-transplantation within 60 days or allo-transplantation within 90 days before the first dose of study drug； >1 grade graft-versus-host disease (GVHD) or using GVHD control medicines that are not allowed by this trial；
  5. Major surgery or serious trauma within 4 weeks before the first dose of study drug.；
  6. anti-tumor agents within 4 weeks before the first dose of study drug（such as chemotherapy, radiotherapy, immunotherapy, target therapy and other clinical research）；Use of Chinese Herbal within 2 weeks before the first dose of study drug；use of Glucocorticoids to anti tumor within 7 days before the first dose of study drug（equivalent to prednisone>20 mg/d）；
  7. Has known active infection with hepatitis B virus or hepatitis C virus（HBV DNA≥2×10\^3 IU/mL，HCV RNA≥10\^3 IU/mL）and liver dysfunction，need the intervention of anti-virus therapy;
  8. Immunocompromised (i.e. has congenital immunodeficiency), including subjects known history of infection with human immunodeficiency virus (HIV) or has known active infection with tubercle bacillus；
  9. Has an active infection or has a temperature > 38.5°C with unknown reasons（Investigators will decide the enrollment of participants with a fever that contributed to tumors）；
  10. Has cardiovascular impairment，including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, or stroke within 1 year prior to the planned first dose of study drug; or ventricular cardiac arrhythmia requiring medical treatment；
  11. abnormal of ECG with clinical significance：such as prolongation of corrected QT interval using Fridericia's formula (QTcF)(male > 450 ms、female> 470 ms）；
  12. History of cerebrovascular accident or transient ischemic attack within 6 months；
  13. Has a prior malignancy other than the malignancies under study within 2 years- EXCEPTION: A subject with a history of a completely resected skin basal cell carcinoma, skin squamous-celled carcinoma, in situ cervical cancer or other in situ carcinomas, and has been relapse-free for 5 years；
  14. Has serious acute/chronic disease or psychic disease，such as suicide intention or action in resent 1 year; or there are abnormal conditions that will increase the risk of using or managing study drug or affect the assessment of study results or investigator's judgment；
  15. Staffs of institute sites directly related to the study or their family members, subordinates. Staffs of the sponsor pharmaceuticals company that directly related to the study；
  16. Females who are pregnant or breastfeeding.
  17. Inability to take oral medication, or any uncontrolled gastrointestinal condition (e.g., active gastroenteritis, chronic diarrhea, known diverticulosis, history of gastrectomy or gastric banding) that might impair the bioavailability of study drug. gastroesophageal reflux disease treated with proton pump inhibitors is eligible（should be no drug interaction）;
  18. Use of known median or potent CYP3A4 or CYP3A5 inducers/inhibitors or P-gp inhibitors.
  19. Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
272 participants (actual)

Study arms

  • Experimental
    SHR2554 treated group

    Part I：treated with escalated doses of EZH2 inhibitor SHR2554 respectively； Part II：treated with fixed dose (RP2D) SHR2554 respectively

    Drug: SHR2554

Interventions

  • DrugSHR2554

    SHR2554 is a selective small molecule inhibitor of the histone-lysine methyltransferase EZH2.

    Also known as: EZH2 Inhibitor

06

What researchers measure

Primary outcomes

  1. Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability])（Part I）

    The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of SHR2554 will be assessed.

    Time frame: through study completion, an average of about 6 months

  2. Recommended phase 2 dose (RP2D)（Part I）

    Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) will be established according to the incidence of dose-limiting toxicities (DLTs) of escalated doses of SHR2554.

    Time frame: 30 days since the date of first dose

  3. Objective response rate (ORR)（Part II）

    assessed by independent radiology review committee (IRC)

    Time frame: 60 days since the date of first dose

Secondary outcomes

  1. Time to peak (Tmax)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Time to peak (Tmax) of plasma concentration

    Time frame: Day 1 and Day 2 of the single dose

  2. Maximum plasma concentration (Cmax)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Maximum plasma concentration (Cmax)

    Time frame: Day 1 and Day 2 of the single dose

  3. Halflife (T1/2)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Halflife (T1/2)

    Time frame: Day 1 and Day 2 of the single dose

  4. Clearance/ bioavailability (CL/F)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Clearance/ bioavailability (CL/F)

    Time frame: Day 1 and Day 2 of the single dose

  5. apparent volume of distribution/bioavailability (Vd/F)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): apparent volume of distribution/bioavailability (Vd/F)

    Time frame: Day 1 and Day 2 of the single dose

  6. Area under curve (AUC)

    Pharmacokinetics profile of a single dose SHR2554 and its metabolite (plasma): Area under curve (AUC)

    Time frame: Day 1 and Day 2 of the single dose

  7. Area under curve, steady state (AUCss)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Area under curve, steady state (AUCss)

    Time frame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  8. Maximum plasma concentration, steady state (Cmax,ss)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Maximum plasma concentration, steady state (Cmax,ss)

    Time frame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  9. Time to peak, steady state (Tmax,ss)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Time to peak, steady state (Tmax,ss)

    Time frame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  10. Halflife (T1/2)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Halflife (T1/2)

    Time frame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  11. Apparent volume of distribution, steady state/bioavailability (Vss/F)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Apparent volume of distribution, steady state/bioavailability (Vss/F)

    Time frame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  12. Clearance/ bioavailability (CL/F)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Clearance/ bioavailability (CL/F)

    Time frame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  13. Accumulation index (Rac)

    Pharmacokinetics profile of continuous medication of SHR2554 and its metabolite (plasma): Accumulation index (Rac)

    Time frame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

  14. Objective response rate (ORR)

    Assess the response rate of subjects to the treatment of SHR2554

    Time frame: every 8 weeks through study completion, an average of about 6 months

  15. Progression-free survival (PFS)

    Assess the survival condition of the subjects after the treatment of SHR2554

    Time frame: every 8 weeks through study completion, an average of about 6 months

  16. Duration of Response (DoR)

    Assess the duration of complete/partial response after the treatment of SHR2554

    Time frame: every 8 weeks through study completion, an average of about 6 months

  17. Time to response（TTR）（Part II only）

    Assess the time to initial response of subjects to the treatment of SHR2554

    Time frame: 60 days since the date of first dose

  18. OS（overall survival）（Part II only）

    Assess the overall survival of subjects treated by SHR2554

    Time frame: 2 years since the date of first dose

Other outcomes

  1. Effect of escalated doses of SHR2554 on the histone H3 lysine 27 trimethylation (H3K27me3) level（Part I-exploratory endpoints）

    Analyze the level of H3K27me3 in the peripheral blood mononuclear cells of the subjects before and after the treatment of escalated doses of SHR2554.

    Time frame: day 1 of the single dose to day 1 of continuous medication cycle 2

  2. EZH2 gene mutation（Part I-exploratory endpoints）

    Assess the known mutation of EZH2 gene in tumor cells or tissues, analyze the relationship between efficacy and EZH2 mutation

    Time frame: within 2 weeks after the last dose

  3. EZH2 expression level（Part I-exploratory endpoints）

    Assess EZH2 expression level in tumor tissues, analyze the relationship between efficacy and EZH2 expression level

    Time frame: within 2 weeks after the last dose

07

Study locations

1 site
  • Beijing Cancer Hospital, Peking University
    Beijing, Beijing Municipality, China
08

References and documents

Publications

  • Song Y, Jin Z, Li ZM, Liu Y, Li L, He C, Su H, Zhou H, Li K, Hao S, Zuo X, Wu J, Li D, Wu M, Sun X, Qi J, Cai Z, Li Z, Li Y, Huang Y, Shen J, Xiao Z, Zhu J. Enhancer of Zeste Homolog 2 Inhibitor SHR2554 in Relapsed or Refractory Peripheral T-cell Lymphoma: Data from the First-in-Human Phase I Study. Clin Cancer Res. 2024 Apr 1;30(7):1248-1255. doi: 10.1158/1078-0432.CCR-23-2582. PubMed 38190117 ↗
  • Song Y, Liu Y, Li ZM, Li L, Su H, Jin Z, Zuo X, Wu J, Zhou H, Li K, He C, Zhou J, Qi J, Hao S, Cai Z, Li Y, Wang W, Zhang X, Zou J, Zhu J. SHR2554, an EZH2 inhibitor, in relapsed or refractory mature lymphoid neoplasms: a first-in-human, dose-escalation, dose-expansion, and clinical expansion phase 1 trial. Lancet Haematol. 2022 Jul;9(7):e493-e503. doi: 10.1016/S2352-3026(22)00134-X. PubMed 35772429 ↗

Individual participant data

Plan to share: Undecided

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 1, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03603951
Lead sponsor
Jiangsu HengRui Medicine Co., Ltd.
Collaborators
Peking University Cancer Hospital & Institute
Responsible party
Sponsor
First posted
Jul 27, 2018
Start date
Aug 14, 2018
Primary completion
Feb 14, 2026 (estimated)
Completion
Aug 14, 2026 (estimated)
Last update
Oct 1, 2024

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is status unknown, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Zeprumetostat

Other studies in this condition

Recurrence →

Other studies from this sponsor

Jiangsu HengRui Medicine Co., Ltd. →

Start the discussion